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Open AccessArticle

Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels

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Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico
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Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico
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Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico
4
Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 4995; https://doi.org/10.3390/ijms20204995
Received: 17 August 2019 / Revised: 5 October 2019 / Accepted: 6 October 2019 / Published: 9 October 2019
(This article belongs to the Section Molecular Pharmacology)
Hyperpolarization-activated cationic HCN channels comprise four members (HCN1–4) that control dendritic integration, synaptic transmission and action potential firing. In the kidney, HCN1, HCN2 and HCN3 are differentially expressed and contribute to the transport of sodium, potassium (K+) and ammonium into the nephrons. HCN3 is regulated by K+ diets in the kidney. In this work we performed a proteomic analysis of HCN3 expressed in human embryonic kidney cells (HEK293 cells). More than 50% of the interacting proteins belonged to mitochondria. Therefore, we explored the presence of HCN channels in kidney mitochondria. By immunoblotting and immunogold electron microscopy HCN3 protein expression was found in rat kidney mitochondria; it was also confirmed in human kidney. Patch-clamp recordings of renal mitochondria and mitochondria from HEK293 cells overexpressing HCN1, HCN2 and HCN3 channels, stained with MitoTracker Green FM, indicated that only HCN3 could produce inwardly K+ currents that were inhibited by ZD7288, a specific blocker of HCN channels. Furthermore, ZD7288 caused inhibition of the oxygen consumption coupled to ATP synthesis and hyperpolarization of the inner mitochondrial membrane. In conclusion, we show for the first time that pacemaker HCN channels contribute to K+ transport in mitochondria facilitating the activity of the respiratory chain and ATP synthesis by controlling the inner mitochondrial membrane potential. View Full-Text
Keywords: mitochondria; kidney; mitochondrial potassium channel; hyperpolarization-activated cyclic nucleotide-gated cationic HCN channels in mitochondria; potassium transport in mitochondria; mitochondria uncoupling mitochondria; kidney; mitochondrial potassium channel; hyperpolarization-activated cyclic nucleotide-gated cationic HCN channels in mitochondria; potassium transport in mitochondria; mitochondria uncoupling
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León-Aparicio, D.; Salvador, C.; Aparicio-Trejo, O.E.; Briones-Herrera, A.; Pedraza-Chaverri, J.; Vaca, L.; Sampieri, A.; Padilla-Flores, T.; López-González, Z.; León-Contreras, J.C.; Hernández-Pando, R.; Escobar, L.I. Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels. Int. J. Mol. Sci. 2019, 20, 4995.

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